Iodine → HCID 86701257, compound

HRID 2276059Notes

Reaction equation

HRID 2276059 reaction equation
II.[C:3]([O:8][C@@H:9]1[C@@H:17]([CH2:18]I)[C:16](=[O:20])[O:15][CH2:14][C@H:13]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:12](=[O:29])[O:11][C@H:10]1[CH3:30])(=[O:7])[CH:4]([CH3:6])[CH3:5].[F:31][C:32]1[CH:37]=[CH:36][C:35](I)=[CH:34][CH:33]=1>CN(C=O)C.CCOC(C)=O.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:3]([O:8][C@@H:9]1[C@@H:17]([CH2:18][C:35]2[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=2)[C:16](=[O:20])[O:15][CH2:14][C@H:13]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:12](=[O:29])[O:11][C@H:10]1[CH3:30])(=[O:7])[CH:4]([CH3:6])[CH3:5]

Participants

8

Reactant 3

HCID 807IodineHCID 96054-FluoroiodobenzeneHCID 86701255HCID 86701255, compound

Product 1

HCID 86701257HCID 86701257, compoundYield 38%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
22 °C

Procedure

To a suspension of freshly ground zinc dust (139 mg, 2.13 mmol) in an oven-dried flask containing a stir bar were added DMF (200 μL; just covered the dust) and iodine (54 mg, 0.21 mmol), and the mixture was stirred for 1 min. To the mixture was added a solution of (3S,6S,7R,8R)-3-(tert-butoxycarbonylamino)-8-(iodomethyl)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate (273 mg, 0.53 mmol) in DMF (1 mL) slowly at 40° C. After 15 min, the reaction mixture was cooled to ambient temperature (about 22° C.) and a solution of Pd2(dba)3 (12 mg, 0.01 mmol), (o-tol)3P (16 mg, 0.05 mmol), and 1-fluoro-4-iodobenzene (80 μL, 0.69 mmol) in DMF (900 μL) was added to the reaction and the reaction was warmed back to 40° C. and stirring continued for 1.5 hr. The mixture was cooled, diluted with EtOAc (2 mL), and filtered through a 0.45 micrometer (μm) fritted filter disc. The solution was diluted with EtOAc (100 mL), washed with H2O (3×), dried over MgSO4, filtered, and concentrated. Purification by column chromatography (SiO2, 0→20% EtOAc/hexanes) gave the title compound (96 mg, 38%) as a white, glassy solid: mp 58-66° C.; 1H NMR (300 MHz, CDCl3) δ 7.08 (m, 2H), 6.95 (m, 2H), 5.22-5.14 (m, 3H), 4.93 (m, 1H), 4.80 (m, 1H), 3.46 (m, 1H), 3.00-2.80 (m, 2H), 2.64 (m, 2H), 1.44 (s, 9H), 1.31 (d, J=6.4 Hz, 3H), 1.25 (d, J=7.0 Hz, 3H), 1.25 (d, J=7.0 Hz, 3H); ESIMS m/z 503.3 ([M+Na]+).

Workup

  1. additioncontaining a stir bar
  2. waitAfter 15 min
  3. temperaturethe reaction was warmed back to 40° C.
  4. stirringstirring
  5. waitcontinued for 1.5 hr
  6. temperatureThe mixture was cooled
  7. filtrationfiltered through a 0.45 micrometer (μm) fritted filter disc
  8. additionThe solution was diluted with EtOAc (100 mL)
  9. washwashed with H2O (3×)
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by column chromatography (SiO2, 0→20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-91501a84387f41c1bada254e90085670
Source dataset
uspto-grants-2015_09
Patent number
US09131690B2

Reaction notes

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